- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00237185
A Study of the Efficacy and Safety of Imatinib Mesylate in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing C-kit Gene
August 14, 2014 updated by: Novartis Pharmaceuticals
Open, Randomized, Phase II Study of Glivec in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing C-kit Plus 10 Year Extension Study
In the core study, participants with unresectable or metastatic gastrointestinal stromal tumors expressing c-kit were treated with either 400 mg or 600 mg imatinib mesylate for 3 years.
The 10 year extension study allowed participants, who successfully completed the core study, to continue study treatment with imatinib mesylate provided they still benefited from treatment and did not demonstrate safety concerns as per the investigator's opinion.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
148
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Victoria
-
Geelong, Victoria, Australia, 3220
- Novartis Investigative Site
-
-
-
-
-
Helsinki, Finland, FIN-00029
- Novartis Investigative Site
-
-
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Dana Farber Cancer Institute Dept of Sarcoma Oncology
-
-
Oregon
-
Portland, Oregon, United States, 97201
- Oregon Health Sciences University Dept. of Oregon Health Sci.
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19111
- Fox Chase Cancer Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Men and non-pregnant women ≥18 years of age with the histopathologically documented diagnosis of malignant GIST that was unresectable and/or metastatic. Confirmation of KIT (CD117) expression via immunohistochemical analysis of tumor sample was also required
- At least one measurable lesion, as defined by Southwestern Oncology Group (SWOG) Solid Tumor Response Criteria, which had not been previously embolized or irradiated
- Performance status ≤3 as defined by the Eastern Cooperative Oncology Group (ECOG) criteria, as well as a life expectancy ≥6 months and adequate end organ function defined as follows: Total bilirubin <1.5 times upper limit of normal (ULN), aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) <2.5 x ULN (or <5 x ULN if hepatic metastases were present), creatinine <1.5 x ULN, absolute neutrophil count (ANC) >1.5 x 10^9/L, platelet count >100 x 10^9/L
Exclusion Criteria:
- Patients with fewer than five years of disease-free survival from any other (non-GIST) malignancy except if the other malignancy was not currently clinically significant and did not require active intervention or if the other malignancy was a basal cell skin cancer or a cervical carcinoma in situ
- Patients with known brain metastases
- Evidence of any of the following disorders: Grade III/IV cardiac failure as defined by the New York Heart Association Criteria, severe concomitant disease, acute or known chronic liver disease (i.e. chronic active hepatitis, cirrhosis) or HIV infection
- Chemotherapy or other investigational therapy within four weeks prior to study entry (six weeks for nitrosourea or mitomycin-C) and/or radiotherapy to ≥25% of the bone marrow
- Inability to cooperate
- Major surgery within two weeks or exposure to other investigational agents within 28 days of entry into the study
Other protocol-defined inclusion / exclusion criteria may have applied.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: imatinib mesylate 400 mg
400 mg once daily
|
Participants were randomized 1:1 to receive imatinib mesylate 400 mg/day or 600 mg/day.
Upon unsatisfactory treatment effect on the starting dose of 400 mg/day or 600 mg/day imatinib mesylate, in the opinion of the treating physician, a dose increase up to 600 mg/day or 800 mg/day, was allowed provided that the participant continued to benefit from the treatment and in the absence of safety concerns.
Other Names:
|
Experimental: imatinib mesylate 600 mg
600 mg once daily
|
Participants were randomized 1:1 to receive imatinib mesylate 400 mg/day or 600 mg/day.
Upon unsatisfactory treatment effect on the starting dose of 400 mg/day or 600 mg/day imatinib mesylate, in the opinion of the treating physician, a dose increase up to 600 mg/day or 800 mg/day, was allowed provided that the participant continued to benefit from the treatment and in the absence of safety concerns.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Best Tumor Response (Core)
Time Frame: Month 36
|
Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria.
Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable.
Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response.
Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.
|
Month 36
|
Best Tumor Response (Core + Extension)
Time Frame: Month 156
|
Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria.
Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable.
Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response.
Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.
|
Month 156
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival (Core)
Time Frame: Date of first imatinib dose to the date of death during the core period, up to 36 months.
|
Overall survival was analyzed as time to event for all participants.
Participants who did not die were censored at the last date known alive, which is the last date of any study medication, laboratory sample, tumor assessment, adverse event end date or date of last contact.
|
Date of first imatinib dose to the date of death during the core period, up to 36 months.
|
Overall Survival (Core + Extension)
Time Frame: Date of first imatinib dose to the date of death during the core and extension periods, up to 156 months.
|
Overall survival was analyzed as time to event for all participants.
Participants who did not die were censored at the last date known alive, which is the last date of any study medication, laboratory sample, tumor assessment, adverse event end date or date of last contact.
|
Date of first imatinib dose to the date of death during the core and extension periods, up to 156 months.
|
Duration of Response (Core)
Time Frame: Date of confirmed best PR or CR to date of confirmed disease progression during the core period, up to 36 months.
|
Duration of response was analyzed as time to event for all participants whose best response was at least a PR.
The onset of response was the first tumor assessment that was subsequently confirmed to constitute at least a partial best response.
The end of response was the first tumor assessment noting PD.
|
Date of confirmed best PR or CR to date of confirmed disease progression during the core period, up to 36 months.
|
Duration of Response (Core + Extension)
Time Frame: Date of confirmed best PR or CR to date of confirmed disease progression during the core and extension periods, up to 156 months
|
Duration of response was analyzed as time to event for all participants whose best response was at least a PR.
The onset of response was the first tumor assessment that was subsequently confirmed to constitute at least a partial best response.
The end of response was the first tumor assessment noting PD.
|
Date of confirmed best PR or CR to date of confirmed disease progression during the core and extension periods, up to 156 months
|
Progression Free Survival (PFS) (Core + Extension)
Time Frame: Date of first imatinib dose to earliest date of progression, resection due to safety/progression, death due to any cause or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.
|
Progression free survival was analyzed as a time to event for each participant.
If a participant had no event, then the PFS was censored at the last tumor assessment.
|
Date of first imatinib dose to earliest date of progression, resection due to safety/progression, death due to any cause or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.
|
Time to Treatment Failure (Core)
Time Frame: Date of first imatinib dose to date of earliest occurrence of progression, death due to any cause, or discontinuation from the trial for any reason other than the condition no longer required therapy during the core period, up to 36 months.
|
Time to treatment failure was analyzed as time to event for all participants.
Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis ate the time of their last tumor assessment.
|
Date of first imatinib dose to date of earliest occurrence of progression, death due to any cause, or discontinuation from the trial for any reason other than the condition no longer required therapy during the core period, up to 36 months.
|
Time to Treatment Failure (Core + Extension)
Time Frame: Date of first imatinib dose to date of earliest occurrence of progression, death due to any cause, or discontinuation from the trial for any reason other than the condition no longer required therapy during the core and extension periods, up to 156 month.
|
Time to treatment failure was analyzed as time to event for all participants.
Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis at the time of their last tumor assessment.
|
Date of first imatinib dose to date of earliest occurrence of progression, death due to any cause, or discontinuation from the trial for any reason other than the condition no longer required therapy during the core and extension periods, up to 156 month.
|
Time to Onset of Response (Core)
Time Frame: Date of first imatinib dose to the date of the first tumor assessment that was later confirmed to be at least a partial response during the core period, up to 36 months.
|
Time to response was analyzed as time to event for all participants.
Participants who did not meet the definition of confirmed PR/CR were censored at the time of their last progression-free tumor assessment.
|
Date of first imatinib dose to the date of the first tumor assessment that was later confirmed to be at least a partial response during the core period, up to 36 months.
|
Time to Onset of Response (Core + Extension)
Time Frame: Date of first imatinib dose to the date of the first tumor assessment that was later confirmed to be at least a partial response during the core and extension periods, up to 156 months.
|
Time to response was analyzed as time to event for all participants.
Participants who did not meet the definition of confirmed PR/CR were censored at the time of their last progression-free tumor assessment.
|
Date of first imatinib dose to the date of the first tumor assessment that was later confirmed to be at least a partial response during the core and extension periods, up to 156 months.
|
Time to Progression (Core + Extension)
Time Frame: Date of first imatinib dose to date of progression or death due to disease indication or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.
|
Time to progression was analyzed as time to event for all participants.
Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis at the time of their last tumor assessment.
|
Date of first imatinib dose to date of progression or death due to disease indication or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2000
Primary Completion (Actual)
June 1, 2013
Study Completion (Actual)
June 1, 2013
Study Registration Dates
First Submitted
October 9, 2005
First Submitted That Met QC Criteria
October 9, 2005
First Posted (Estimate)
October 12, 2005
Study Record Updates
Last Update Posted (Estimate)
August 19, 2014
Last Update Submitted That Met QC Criteria
August 14, 2014
Last Verified
August 1, 2014
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Neoplasms, Connective Tissue
- Gastrointestinal Stromal Tumors
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Imatinib Mesylate
Other Study ID Numbers
- CSTI571B2222
- CSTI571B2222/E1
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumor (GIST)
-
Centre Leon BerardRecruitingMetastatic Gastrointestinal Stromal Tumor | Unresectable Gastrointestinal Stromal Tumor (GIST) | Locally Advanced Gastrointestinal Stromal Tumor (GIST)France
-
Centre Leon BerardRecruitingC-KIT Mutation | Metastatic Gastrointestinal Stromal Tumor (GIST) | Advanced Gastrointestinal Stromal Tumor (GIST)France
-
Hospital Universitario Virgen de la ArrixacaNot yet recruitingLiver Diseases | Liver Transplantation | Liver Neoplasms | Gastrointestinal Stromal Tumors | Metastasis | Liver Metastases | Liver Transplant; Complications | Liver Cancer | Liver Transplant Disorder | Liver Carcinoma | GIST, Malignant | GIST | Metastases | Metastatic Liver Cancer | Gastrointestinal Stromal Tumor of... and other conditionsSpain
-
National Cancer Institute (NCI)CompletedStage III Soft Tissue Sarcoma AJCC v7 | Stage IV Soft Tissue Sarcoma AJCC v7 | Pleomorphic Liposarcoma | Metastatic Undifferentiated Pleomorphic Sarcoma | Metastatic Unresectable Sarcoma | Unresectable Soft Tissue Sarcoma | Metastatic Soft Tissue Sarcoma | Locally Advanced Soft Tissue Sarcoma | Metastatic... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedMetastatic Melanoma | Advanced Malignant Solid Neoplasm | Metastatic Malignant Solid Neoplasm | Unresectable Melanoma | C-KIT Tyrosine Kinase Protein Overexpression | Clinical Stage IV Cutaneous Melanoma AJCC v8 | Metastatic Gastrointestinal Stromal Tumor | Pathologic Stage IV Cutaneous Melanoma... and other conditionsUnited States
-
IDRx, Inc.RecruitingGastrointestinal Diseases | Metastatic Cancer | Digestive System Disease | Gastrointestinal Stromal Tumor (GIST)United States, Belgium, Germany, Spain
-
Ascentage Pharma Group Inc.HealthQuest Pharma Inc.RecruitingSolid Tumor, Adult | Gastrointestinal Stromal Tumor (GIST)China
-
Xinhua Zhang, MDXijing Hospital; Chongqing University Cancer Hospital; Xiangya Hospital of Central... and other collaboratorsNot yet recruitingGastrointestinal Stromal Tumors | Unresectable Solid Tumor | Recurrent Metastatic Malignant Neoplasm
-
Centre Leon BerardBlueprint Medicines CorporationActive, not recruitingGIST, Malignant | GIST | PDGFR-Alpha D842VFrance
-
SCRI Development Innovations, LLCNovartis PharmaceuticalsCompletedMetastatic or Unresectable Solid Tumor MalignancyUnited States
Clinical Trials on Imatinib mesylate
-
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.CompletedChronic Myeloid LeukemiaChina
-
Institut BergoniéNovartisTerminatedLeukemia, Myeloid, Chronic-PhaseFrance
-
Scandinavian Sarcoma GroupCompleted
-
Sarit AssoulineNovartisRecruitingChronic Myeloid Leukemia | Chronic Myeloid Leukemia in Remission | Chronic Myeloid Leukemia, BCR/ABL-PositiveCanada
-
Novartis PharmaceuticalsCompletedProgressive Gastrointestinal Stromal TumorGermany
-
Novartis PharmaceuticalsCompletedLife Threatening Diseases
-
UNICANCERCompletedDesmoid TumorFrance
-
University Hospital, BordeauxNovartis; Ministry of Health, FranceCompletedScleroderma, Systemic | Scleroderma, LocalizedFrance
-
Maisonneuve-Rosemont HospitalHippocrate Research & DevelopmentUnknownGastrointestinal Stromal TumorsCanada